Trends and outcomes of pancreaticoduodenectomy for periampullary tumors: A 25-year single-center study of 1000 consecutive cases

Table 1 Demographic and preoperative data

Variable	Total,n = 1000	First 10 yr,1993-2002	Second 10 yr,2003-2012	Last 5 yr,2013-2017	P-value
Age in yr	54 (12-88)	53	55	55	0.22
Sex
Male	614 (61.4)	190 (63.3)	260 (58.8)	164 (63.6)	0.33
Female	386 (38.6)	110 (36.7)	182 (41.2)	94 (36.4)
DM	145 (14.5)	39 (13)	60 (13.6)	46 (17.8)	0.21
BMI in kg/m2
< 25	723 (72.3)	250 (38.3)	326 (73.8)	147 (57)	0.0001
> 25	277 (27.7)	50 (16.7)	116 (26.2)	111 (43)
Abdominal pain	753 (75.3)	230 (76.7)	329 (74.4)	194 (74.2)	0.12
Jaundice	909 (90.9)	265 (88.3)	406 (91.9)	238 (92.2	0.18
Preoperative biliary drainage	511 (51.1)	163 (54.5)	226 (51.1)	122 (47.3)	0.23
Preoperative serum albumin in mg	4 (3.2-5.2)	4.1	4	3.9	0.23
Preoperative serum bilirubin in mg	4 (0.5-38)	3.1	4.7	4.3	0.0001
Preoperative CEA	6.4 (0.5-394)	8	8	6	0.09
Preoperative CA19-9	27 (0.5-1200)	32	33	34	0.12

Data are presented as n (%) or n (range), unless otherwise indicated. BMI: Body mass index; CEA: Carcinoembryonic antigen; DM: Diabetes mellitus.

Table 2 Operative data

Variable	Total, n = 1000	First 10 yr, 1993-2002	Second 10 yr, 2003-2012	Last 5 yr, 2013-2017	P-value
Cirrhosis	129 (12.9)	28 (9.3)	62 (14)	39 (15.1)	0.009
Mass size in cm	3 (0.5-15)	3	3	3
< 2	418 (41.8)	123 (41)	174 (39.4)	123 (46.9)	0.14
> 2	582 (58.2)	177 (59)	268 (60.6)	137 (53.1)
Pancreatic texture
Soft	596 (59.6)	190 (63.3)	263 (59.5)	143 (55.4)	0.23
Firm	404 (40.4)	110 (36.7)	179 (40.5)	115 (44.6)
Median pancreatic duct diameter in mm	5 (1-15)				0.47
< 3	313 (31.3)	97(32.3)	137 (30.9)	79 (30.6)
> 3	687 (68.7)	20367.7)	305 (60.1)	179 (69.4)
Pancreatic duct to posterior border in mm					0.45
< 3	421 (42.1)	128 (42.7)	185 (41.9)	108 (41.9)
> 3	579 (57.9)	172 (57.3)	257 (58.1)	150 (58.1)
Pancreatic stump mobilization in cm	2 (1-4)	2	2	2	0.45
CBD diameter in mm	15 (5-30)	15	15	15	0.06
Type of reconstruction
PG	791 (79.1)	235 (78.3)	417 (94.3)	139 (53.9)	0.0001
Simple PJ	163 (16.3)	65 (21.7)	25 (5.7)	73 (28.3)
Isolated loop PJ	46 (4.6)	0	0	46 (17.8)
Duct to mucosa	134 (13.4)	9 (3)	65 (14.7)	60 (23.3)
Invaginated type with duct to mucosa	644 (64.4)	234 (78)	250 (65.6)	160 (62)	0.0001
Invaginated type without duct to mucosa	221 (22.1)	57 (19)	126 (28.5)	38 (14.7)
No anastomosis	1 (0.1)	0	1 (0.2)	0
Standard approach	908 (90.8)	277 (92.3)	388 (87.8)	243 (94.7)	0.004
Posterior approach	92 (9.2)	23 (7.7)	54 (12.2)	15 (5.8)
Complete meso-pancreatectomy	574 (57.4)	83 (27.7)	233 (52.7)	258 (100)	0.0001
Laparoscopic assisted PD	11 (1.1)	0	0	11 (4.3)	0.0001
Complete laparoscopic PD	10 (1)	0	0	10 (3.9)
Vascular resection	12 (1.2)	0	4 (0.9)	8 (3.1)	0.003
Primary anastomosis	0	0	3 (0.7)	8 (3.1)
Gortex	0	0	1 (0.2)	0
Operative time in h	5 (3.5-10)	6	5	5	0.001
Blood loss in cc	500 (50-4000)	500	400	300	0.001

Data are presented as n (%) or n (range). PD: Pancreaticoduodenectomy; PG: Pancreaticogastrostomy; PJ: Pancreaticojejunostomy.

Table 3 Postoperative data

Variable	Total,n = 1000	First 10 yr,1993-2002	Second 10 yr,2003-2012	Last 5 yr,2013-2017	P-value
Hospital stay in d	8 (5-71)	9	8	8	0.0001
Time to oral intake in d	5 (4-56)	6	5	5	0.33
Total amount of drainage in mL	700 (40-35000)	1200	600	600	0.0001
Drain removal in d	8 (4-71)	8	8	8	0.03
Total postoperative complications	323 (32.3)	120 (40)	131 (29.6)	72 (27.9)	0.02
Dindo grade
I	114 (11.4)	24	47	43
II	97 (9.7)	40	45	12	0.11
III	69 (6.9)	36	24	9
IV and V	43 (4.3)	20	15	8
Severe complications, ≥ III
Minor	211 (21.1)	84	92	55	0.23
Major	109 (10.9)	56	69	17
Pancreatic fistula	139 (13.9)	45 (15)	56 (12.7)	38 (14.7)	0.01
Grade A	67 (6.7)	14	33	20	0.04
Grade B	48 (4.8)	20	17	11
Grade C	24 (2.4)	11	6	7
DGE	180 (18)	76 (25.3)	67 (15.2)	37 (14.3)	0.06
Types of DGE
Secondary DGE	152 (15.2)	70 (23.3)	54 (12.2)	27 (10.5)	0.03
Primary DGE	28 (2.8)	5 (1.7)	13 (2.9)	10 (3.9)
Pulmonary complications	46 (4.6)	20 (6.7)	21 (4.8)	5 (1.6)	0.01
Bile leak	73 (7.3)	39 (13)	19 (4.3)	15 (5.8)	0.001
Postoperative bleeding	25 (2.5)	13 (4.3)	7 (1.6)	5 (1.9)	0.49
Pancreatitis	20 (2)	12 (4.3)	7 (1.6)	1 (0.4)	0.004
Bleeding PG	15 (1.5)	8 (2.7)	5 (1.2)	2 (0.8)	0.14
Wound infection	50 (5)	13 (4.6)	25 (5.7)	12 (4.7)	0.77
Re-operation	74 (7.4)	25 (8.3)	33 (7.5)	16 (6.2)	0.21
Recurrence	321 (36.9)	130 (50.4)	125 (32.6)	66 (28.7)	0.0001
Hospital mortality	43 (4.3)	20 (6.6%)	15 (3.4)	8 (3.1)	0.02
Postoperative chemoradiotherapy	275 (27.5)	0	132 (29.9)	143 (55.4)	0.0001
Overall median survival in mo	26 (1-300)	21	30	37	0.0001
1 yr	90%	87%	93%	87%
3 yr	33%	19%	37%	64%
5 yr	19%	11%	21%

Data are presented as n (%) or n (range), unless otherwise indicated. DGE: Delayed gastric emptying; PG: Pancreaticogastrostomy.

Table 4 Univariate and multivariate analyses of risk factors of development of post-operative pancreatic fistula

	Univariate	Multivariate	Exp(B)	95%CI for Exp(B)
	P-value	P-value		Lower	Upper
Age grouping > 60 yr	0.2
Sex	0.99
DM	0.58
BMI >25 kg/m2	0.0001	0.0001	6.468	4.193	9.977
Preoperative serum bilirubin > 10 mg%	0.62
Preoperative ERCP	0.52
Liver cirrhosis	0.05	0.328	0.699	0.341	1.434
Size of the tumor > 2 cm	0.91
Soft pancreas	0.0001	0.0001	0.218	0.14	0.341
Pancreatic duct diameter > 3 mm	0.0001	0.0001	0.182	0.118	0.279
Pancreatic duct closely related to posterior border of pancreas > 3 mm	0.0001	0.0001	0.372	0.243	0.57
Blood loss > 1000 mL	0.67
Blood transfusion	0.94
Type of pancreatic reconstruction	0.62
Duration of operation	0.75
Site of the tumor	0.34
Period of the study	0.001	0.001	0.615	0.461	0.82

BMI: Body mass index; DM: Diabetes mellitus; ERCP: Endoscopic retrograde cholangiopancreatography.

Table 5 Postoperative pathology n (%)

Variable	Total,n = 1000	First 10 yr,1993-2002	Second 10 yr,2003-2012	Last 5 yr,2013-2017
Site of the tumor
Ampullary tumor	312 (31.2)	92 (30.7)	145 (32.8)	75 (29)
Pancreatic head mass	556 (55.6)	171 (57)	257 (58.1)	128 (49.6)	0.0001
CBD duct tumor	41 (4.1)	16 (5.3)	13 (2.9)	12 (4.7)
Duodenal tumor	61 (6.1)	20 (6.7)	27 (6.1)	14 (5.4)
Uncinate process mass	30 (3)	1 (0.3)	0	29 (11.3)
Pathological diagnosis
Adenocarcinoma	836 (83.6)	250 (83.3)	357 (80.7)	229 (88.8)
Undifferentiated carcinoma	20 (2)	1 (1.7)	19 (4.3)	0
Papillary cystadenocarcinoma	6 (0.6)	4 (1.3)	2 (0.5)	0	0.0001
Lymphoma	4 (0.4)	2 (0.6)	2 (0.5)	0
Neuroendocrine tumor	28 (2.8)	12 (4)	10 (2.3)	6 (2.3)
Solid pseudopapillary tumor	20 (2)	5 (1.7)	8 (1.8)	7 (2.7)
Chronic pancreatitis	24 (2.4)	6 (2)	14 (3.2)	4 (1.6)
Benign cyst	12 (1.2)	3 (1)	8 (1.8)	1 (0.4)
Adenoma with dysplasia	41 (4.1)	15 (5)	19 (4.3)	7 (2.7)
Gastrointestinal stromal tumor	2 (0.2)	0	1 (0.2)	1 (0.4)
Glomus	1 (0.1)	1 (0.3)	0	0
Adenosquamous	2 (0.2)	1 (0.3)	1 (0.2)	0
Pleomorphic adenoma	1 (0.1)	0	1(0.2)	0
Adenomyoma	3 (0.3)	0	0	3 (1.2)
Malignant	870 (87)	258 (86)	382 (86.4)	230 (89.1)	0.38
Borderline	48 (4.8)	17(5.7)	18 (4.1)	13 (5.1)
benign	82 (8.2)	25 (8.3)	42 (9.5)	15 (5.8)
Number of dissected lymph node	6 (0-40)	5 (0-18)	6 (0-40)	6 (0-40)	0.59
Number of lymph node infiltration	0 (0-14)	0 (0-3)	0 (0-14)	0 (0-14)	0.07
Perineural infiltration	187 (18.7)	62 (20.7)	75 (17)	50 (19.9)	0.09
Perivascular infiltration	134 (134)	40 (13.3)	66 (14.9)	28 (10.9)	0.13
Pancreatic safety margin
R1	91 (9.1)	40 (13.3)	41 (9.3)	10 (3.8)	0.01
R2	15 (1.5)	7 (2.3)	6 (1.4)	2 (0.7)